Solution structure of the DNA decamer duplex containing a 3'-T x T basepair of the cis-syn cyclobutane pyrimidine dimer: implication for the mutagenic property of the cis-syn dimer

Nucleic Acids Res. 2000 Apr 15;28(8):1794-801. doi: 10.1093/nar/28.8.1794.

Abstract

The cis - syn dimer is the major DNA photoproduct produced by UV irradiation. In order to determine the origin of the mutagenic property of the cis - syn dimer, we used NMR restraints and molecular dynamics to determine the solution structure of a DNA decamer duplex containing a wobble pair between the 3'-T of the cis - syn dimer and the opposite T residue (CS/TA duplex). The solution structure of the CS/TA duplex revealed that the 3'-T x T base pair of the cis - syn dimer had base pair geometry that was significantly different from the canonical Watson-Crick base pair and caused destabilization and conformational distortion of its 3'-region. However, a 3'-T x A base pair at the cis - syn dimer within this related DNA decamer maintains the normal Watson-Crick base pair geometry and causes little distortion in the conformation of its 3'-side. Our results show that in spite of its stable hydrogen bonding, the insertion of a T residue opposite the 3'-T of the cis - syn dimer is inhibited by structural distortion caused by the 3'-T x T base pair. This may explain why the frequency of the 3'-T-->A transversion, which is the major mutation produced by the cis - syn dimer, is only 4%.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing*
  • DNA / chemistry*
  • Dimerization
  • Magnetic Resonance Spectroscopy
  • Mutagens*
  • Nucleic Acid Conformation*
  • Pyrimidine Dimers / chemistry*
  • Solutions

Substances

  • Mutagens
  • Pyrimidine Dimers
  • Solutions
  • DNA

Associated data

  • PDB/1QL5